High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma

Alessandro Raso, Samantha Mascelli, Roberto Biassoni, Paolo Nozza, Marcel Kool, Angela Pistorio, Elisabetta Ugolotti, Claudia Milanaccio, Sara Pignatelli, Manuela Ferraro, Marco Pavanello, Marcello Ravegnani, Armando Cama, Maria Luisa Garré, Valeria Capra

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Abstract

The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative-polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P =.007) and in those with metastasis (P =.03). Kaplan-Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P =.0004 and P =.002, for OS and PFS for all cases, respectively; P =.002 and P =.008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P =.008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P =.019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.

Original languageEnglish
Pages (from-to)500-508
Number of pages9
JournalNeuro-Oncology
Volume13
Issue number5
DOIs
Publication statusPublished - May 2011

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Medulloblastoma
Disease-Free Survival
Survival
Neoplasm Metastasis
Gene Expression
Messenger RNA
Neoplastic Stem Cells
Kaplan-Meier Estimate
Microarray Analysis
Transcriptome
Proportional Hazards Models
Glioma
Coloring Agents
Pediatrics
Polymerase Chain Reaction
Neoplasms

Keywords

  • Cancer stem cells
  • Medulloblastoma
  • PROM1
  • q-PCR

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

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title = "High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma",
abstract = "The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative-polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P =.007) and in those with metastasis (P =.03). Kaplan-Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P =.0004 and P =.002, for OS and PFS for all cases, respectively; P =.002 and P =.008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P =.008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P =.019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.",
keywords = "Cancer stem cells, Medulloblastoma, PROM1, q-PCR",
author = "Alessandro Raso and Samantha Mascelli and Roberto Biassoni and Paolo Nozza and Marcel Kool and Angela Pistorio and Elisabetta Ugolotti and Claudia Milanaccio and Sara Pignatelli and Manuela Ferraro and Marco Pavanello and Marcello Ravegnani and Armando Cama and Garr{\'e}, {Maria Luisa} and Valeria Capra",
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month = "5",
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language = "English",
volume = "13",
pages = "500--508",
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TY - JOUR

T1 - High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma

AU - Raso, Alessandro

AU - Mascelli, Samantha

AU - Biassoni, Roberto

AU - Nozza, Paolo

AU - Kool, Marcel

AU - Pistorio, Angela

AU - Ugolotti, Elisabetta

AU - Milanaccio, Claudia

AU - Pignatelli, Sara

AU - Ferraro, Manuela

AU - Pavanello, Marco

AU - Ravegnani, Marcello

AU - Cama, Armando

AU - Garré, Maria Luisa

AU - Capra, Valeria

PY - 2011/5

Y1 - 2011/5

N2 - The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative-polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P =.007) and in those with metastasis (P =.03). Kaplan-Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P =.0004 and P =.002, for OS and PFS for all cases, respectively; P =.002 and P =.008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P =.008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P =.019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.

AB - The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative-polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P =.007) and in those with metastasis (P =.03). Kaplan-Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P =.0004 and P =.002, for OS and PFS for all cases, respectively; P =.002 and P =.008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P =.008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P =.019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.

KW - Cancer stem cells

KW - Medulloblastoma

KW - PROM1

KW - q-PCR

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